It is generally assumed by many investigators that neuronal membranes are the primary sites of ethanol action, causing expansion and increasing fluidity of the membrane. In response to the disordering effects of ethanol, membranes may alter their lipid composition and structure to restore the fluidity to that of the naive state, adaptations which may be associated with the development of tolerance and dependence. Biochemical studies so far have failed to pinpoint any particular membrane component(s) to be responsible for changes in membrane fluidity. This may partly be due to the fact that investigators so far have only looked at changes in membrane cholesterol and phospholipid composition. It is of significance that neuronal cells contain a substantial amount of sialic acid, a key component of structural polysaccharides (gangliosides and glycoproteins). Gangliosides are implicated in several brain functions. Acute and chronic ethanol treatments have been shown to alter the number of surface exposed sialic acids in neuronal membranes from rat brain. Studies with spin labeled gangliosides added to liposomes indicate that the mobility of the ganglioside head groups significantly decreased with increasing bilayer concentration of unlabeled gangliosides. Thus it is most likely that gangliosides may regulate the membrane fludity and rigidity. This may be a missing link. Therefore, the proposed research will focus on ethanol-induced changes in surface exposure and composition of glycoconjugates in brain membranes. This study will explore in detail acute and chronic effects of ethanol on a) surface exposure of glycoconjugates following galactose oxidase-sodium borotritide labeling procedure and sodium metaperiodate/sodium borotritide procedure, and b) apparent turnover of membrane sialoglycoconjugates by incorporation studies with radiolabeled N-acetyl-mannosamine, a specific precursor for sialic acid. The studies will be done at a time when animals are behaviorally tolerant to ethanol. These studies will reveal whether or nor neuronal glycoconjugates are responsible for the adaptive process involved in ethanol tolerance and dependence. This will lead to a better understanding of the adaptive mechanism relating ethanol tolerance and dependence.